Major changes take place in the output to respiratory pump and upper airway muscles in association with the phasic events of REM sleep. These phasic changes have adverse consequences and initiate apneas in REM sleep. The overall goal of this proposal is to investigate the neural mechanisms producing these phasic respiratory phenomena. Our attention is directed to the pedunculopontine tegmental (PPT) nucleus in the pons. Lesions of this area abolish ponto-geniculo-occipital (PGO) waves that occur phasically in REM sleep. PGO waves are temporally linked to the phasic changes in respiration in REM sleep. Our goal is to determine the role of neurons in this area in generation of the phasic respiratory phenomena in REM sleep. The first protocol involves lesioning the area by neurotoxic chemicals and examining the effect on PGO waves and respiratory phasic phenomena. If, as we postulate, this area is critical to generating the phasic-changes in respiratory motor output, they should be abolished or markedly reduced in frequency by such lesions. PGO waves and alteration in diaphragm output can also be produced by alerting stimuli; this has led to the concept that there is endogenous activation of the startle system in REM sleep. Thus, in this protocol we will also determine whether lesions of the PPT abolish the PGO and respiratory response to alerting stimuli. In a second series of studies, we will apply complimentary techniques. These will be based on manipulating the neurochemical environment of the region. There are different theories as to what modulates burst neurons that generate PGO waves. One theory implicates serotonin from the dorsal raphe, another serotonin and noradrenaline from locus coeruleus, while a third proposes that GABA from substania nigra plays the major role. The studies we propose will directly test each of these hypotheses. In each case we will administer antagonists in non-REM states to see if we can induce PGO waves and associated phasic respiratory phenomena. Agonists will be administered in REM sleep to see if PGO wave production and phasic respiratory changes can be blocked. Such studies will both enhance our understanding of the role of this area in generating phasic respiratory phenomenon and the fundamental mechanism controlling these phasic generators. Activity of these neural generators must be relayed to the respiratory motor outputs. There are both ascending and descending projections from the area. In order to begin to establish which of these is likely to mediate the respiratory effects, we will, in a third series of protocols, study the effect of interrupting the descending projections on phasic respiratory events. Because activity of neurons in the PPT may also be affected by sleep disruption, the final protocol will address whether a vicious cycle exists whereby interruption of REM sleep leads to more phasic respiratory phenomena. These studies are, therefore, a comprehensive investigation of the mechanism generating phasic respiratory change in REM sleep, their neurochemical control and their relevance to sleep apnea syndrome.